Clonogneic assays measure the ability of single cells to proliferate and form a colony. This process approximates closely the regrowth and recurance of tumors after treatment with radiation or chemotherapy, providing a ready assay to screen for drugs that block this process. Yet, clonogenic assays are laborintensive and too cumbersome for high throughout screening (HTS) of compound libraries. Here we propose to develop a HTS system based on a clonogenic endpoint. A close examination of the literature and our own work shows that all necessary components for an HTS with a clonogenic endpoints already exist through efforts in the industry and academia. We will combine these and validate their utility by comparing with conventional clonogenic assays, to produce an HTS system with defined and validated standared opeating procedures. This system will be transferrable to other laboratories. Potential commercial applications include screening compound libraries for hits with dose-modification for radiation or chemotherapeutics. The HTS system we propose to develop will allow us to identify new compounds with the potential to inhibit regrowth of tumors after treatment. The HTS system will also allow us to rapidly test the efficacy of combining existing drugs or drugs with radiation, thus identifying rational treatment combinations.